The research program of the Chronicity of Viral Infections [CVI] Emerging Team is currently divided in two research axes:
1. Macrophages are durable hosts for viral pathogens via infection of common myeloid progenitors
Chronic inflammation is commonly observed in HIV-infected patients despite antiretroviral treatment and in individuals with post-acute sequelae of COVID-19. We are investigating: i) whether macrophages precursors (common myeloid progenitors) are primed early at the bone marrow stage by a first inflammatory stimulus (e.g. viral primo-infection), displaying thereafter an enhanced inflammatory response upon a second stimulus (e.g. re-infection or superinfection) once they are terminally differentiated into tissue-like macrophages; and ii) whether this trained response is directly implicated in persistent viral replication in tissular macrophages, sustaining infection and chronic inflammation deleterious for the homeostasis.
2. Megakaryocytes targeted by viruses participate in infectious disease progression
Megakaryocytes, precursor of platelets, are gaining momentum in immunology field as inflammatory/immune system actors – a poorly understood but exciting topic in immunology. We will investigate the detrimental consequences of megakaryocyte infection for the immune system and the cellular/molecular mechanisms controlling viral persistent in this myeloid cell. We aim at deciphering the megakaryocyte factors expressed upon viral infections that will be inherited by their daughter platelets and that thereafter will immunomodulate immune cells upon platelet-cell contact. Virus-induced, platelet druggable targets will be functionally assessed by blockage/inhibition using antibodies and CRISPR/Cas9 strategies, in in vitro and in vivo models, opening avenues for novel therapeutical strategies.
Funding: CNRS, Région Hauts-de-France, SIDACTION